tbuckley/cabot-search huggingface dataset:
5627905 TECHNOLOGY ACCESS AND PREFERENCES FOR SMARTPHONE APP INTERVENTION TO OPTIMIZE IRON CHELATION ADHERENCE AMONG ADOLESCENTS, YOUNG ADULTS, AND PARENTS OF INDIVIDUALS RECEIVING CHRONIC TRANSFUSIONS
Authors: P.S. Reddy, M. Locke, K. King, S.M. Badawy
Journal: HemaSphere (2023)

Background: Iron chelation therapy (ICT) is an essential medication for people with thalassemia and other hematological disorders requiring long-term red blood cell transfusion to minimize the risk of iron overload. Suboptimal adherence to iron chelation medication is prevalent and has been associated with increased risk of iron overload, resulting in increased morbidity, mortality, and healthcare utilization. Widespread use of personal technology makes mobile health (mHealth) an attractive platform to promote adherence. Aims: The objective of this study was to examine access to mobile technology and preferences for an mHealth intervention to improve adherence to ICT. Methods: This is an analysis of a cross-sectional survey that was administered through REDCap using tablets during pRBCs transfusion visits at Ann & Robert H. Lurie Children’s Hospital of Chicago. Parents of children receiving chronic transfusions, as well as adolescents and young adults (AYAs) receiving chronic transfusions were enrolled between August 2018 and June 2019. Patients had to have a hematologic diagnosis requiring chronic transfusions, be on an iron chelation therapy, and be 12 years or older to complete the survey. Parents were required to have a child older than 24 months who met these criteria. Results: A total of 60 participants were included (median age [IQR] 31.5 [20-39]; female, 36.7% [40/60]), with a total of 29 parents and 31 patients. The most endorsed mHealth app features among participants, both parents and patients, included laboratory monitoring (91.7%, 55/60), reminders to take ICT (83.3%, 50/60), and education about ICT (81.7%, 49/50). In particular, parents’ most endorsed features included laboratory monitoring (93.1%, 27/29), and education about ICT (86.2%, 25/29) (Figure 1). On the other side, AYA’s most endorsed features included laboratory monitoring (90.3%, 28/31) and reminders to take iron chelation medication (90.3%, 28/31) (Figure 1). There were no significant differences between parents and patients in their preferences, although there was a trend towards a greater proportion of patients compared to parents who preferred positive feedback in the form of encouraging messages when taking medications as an app feature (87.1% vs. 68.96%, p =0.09). Conclusions: Parents and AYAs reported a strong interest in multiple mHealth app features. Participants provided valuable insight into optimal strategies and preferred app features for developing a multifunctional technology-based behavioral intervention (mHealth app), to promote ICT adherence for AYA with thalassemia or other chronic-transfusion dependent conditions.References 1. Badawy et al, Pediatr Blood Cancer 2016;63(5):848-52. 2. Badawy et al, Cochrane Database Syst Rev 2019;6(6):CD012900. 3. Reddy et al, Ann Med 2022;54(1):326-342. 4. Locke et al, Hemoglobin 2022;5:1-13.
5613463 PREVALENCE OF HEMOCHROMATOSIS HFE GENE POLYMORPHISM AMONG EGYPTIAN βTHALASSEMIA PATIENTS AND ITS RELATION TO DEVELOPMENT OF DIABETES MELLITUS
Authors: M. Zakaria, E. Abdel Hamid, N. Rafaat, S. Elsayed
Journal: HemaSphere (2023)

Background: β-thalassemia constitutes a major health problem in Mediterranean countries. Impaired glucose tolerance and diabetes mellitus are observed complications in patients with thalassemia. However, the mechanisms leading to diabetes are still poorly understood.H63D gene polymorphism, is the second variant of hemochromatosis (HFE) gene, that causes hemochromatosis. Aims: We aimed to assess the frequency of diabetes mellitus in β -thalassemia patients and the frequency of H63D gene polymorphism as well as its relation to development prediabetes and diabetes mellitus in β -thalassemia patients. Methods: Case control study was conducted on 50 patients with β-thalassemia and 50 healthy control with matched age and sex. The age ranged from 6-18y. Study subjects were investigated with oral glucose tolerance test, fasting C-Peptide, fasting insulin, anti -gad and screened for frequency of H63D mutation of HFE gene using restriction fragment length polymorphism. Results: 32% of patients had normal glycemic state, 52% had impaired glucose tolerance and 16% were diabetic P<0.001. H63D mutation was more frequent in thalassemia patient. GG genotype was significantly higher in β- thalassemia patients versus healthy controls (68%vs24%) P<0.001. GG genotype was prevalent in 77%and 75% of prediabetes and diabetic thalassemia patients respectively, versus 50% in patients with normal glycemic state P<0.001. Conclusions: GG genotype of H63D mutation of hemochromatosis HFE gene was frequent in our β- thalassemia patients which may be considered as a genetic risk factor for development of impaired glucose tolerance and diabetes in patients with. β-thalassemia. Keywords: thalassemia; diabetes; HFE gene mutation References 1. Azami M et al, Caspian J Intern Med. 2017; 8:1-15. 2. Hashemi A et al, J Shahid Sadoughi Univ Med Sci. 2009;17:220–8.
5613082 CD34+ HEMATOPOIETIC STEM CELL COUNT AS NOVEL BIOMARKER FOR PREDICTING VASCULAR EVENTS IN EGYPTIAN CHILDREN WITH SICKLE CELL DISEASE
Authors: M.A.E. Ellaboudy, N.H.A. Hussien, M.A.I. Ismail, A.A.M. Okba, R.A.I. Ibrahim
Journal: HemaSphere (2023)

Background: Vasoocclusion is the major clinical feature of sickle cell disease (SCD). It results in acute painful vasoocclusive crises and progresses to multiple organ failure (1). Severe SCD is defined as frequent pain, recurrent Acute Chest Syndrome (ACS), stroke and death(2). Therefore, it is essential to identify relevant predictive markers for clinical vascular events. Aim: Evaluation of circulating CD34 as a novel predictive marker of occurrence of vascular events in children with sickle cell disease in their steady state and to relate its levels to other clinical and laboratory parameters of SCD. Methods: 50 patients diagnosed with SCD aged 0.3-13 years old (median 2 years) in their steady state for at least 3 month were enrolled. History with emphasis on neurovascular and peripheral vascular events was taken then hematology, hemolysis, coagulation markers and flow cytometery for quantification of circulating CD34 were withdrawn at inclusion and compared to age and sex matches control then patients were prospectively followed up for 6 months where 2 groups of patients were compared depending on development of vascular events. Results: Results showed statistically significant higher level of circulating CD34+ in patients with SCD compared to control (p <0.001). Patients who developed peripheral vascular events on follow up (n=29) has statistically significant higher level of previous neurovascular events, previous history of vasooclussive crisis(VOC) and previous hospitalization for VOC (p-value 0.015, 0.001 and 0.001 respectively).As for laboratory markers, they have statistically significant higher level of total leucocytic count(TLC), neutrophil count, platelet count and CD34+ level with cut off value of >4340 cell/ ml and higher Time Averaged Mean Flow (TAMMAX)>115cm/sec(p-value 0.015, 0.008, 0.042 and 0.022, 0.028 respectively). There was negative correlation between CD34 and age of diagnosis (p<0.006), hemoglobin level at inclusion (p=0.045), while positively correlated with peripheral vascular events on follow up, TLC, platelet count and bilirubin level at inclusion(p=0.022, 0.01, 0.044, <0.001). Conclusion: Our data showed that circulating CD34 is a potential biomarker for predicting vascular events in children and adolescents with SCD at steady state. References 1. Manwani D and Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood. 2013 Dec 5;122(24):3892-8. 2. Jain S, Bakshi N, Krishnamurti L. Acute Chest Syndrome in Children with Sickle Cell Disease. Pediatr Allergy Immunol Pulmonol. 2017 Dec 1;30(4):191-201
Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA
Authors: Javed Butler, Yinggan Zheng, Muhammad Shahzeb Khan, Diana Bonderman, Lars H. Lund, Christopher R. deFilippi, Robert O. Blaustein, Justin A. Ezekowitz, Cecilia Freitas, Adrian F. Hernandez, Christopher M. O’Connor, Adriaan A. Voors, Cynthia M. Westerhout, Carolyn S.P. Lam, Paul W. Armstrong
Journal: JACC Heart Failure (2023)
Will Knowing More Translate Into More Organs?
Authors: Savitri Fedson
Journal: JACC Heart Failure (2023)

The U.S. heart allocation system ranks candidates with only 6 treatment-based categorical “statuses” and ignores many objective patient characteristics.This study sought to determine the effectiveness of the standard 6-status ranking system and several novel prediction models in identifying the most urgent heart transplant candidates.The primary outcome was death before receipt of a heart transplant. The accuracy of the 6-status system was evaluated using Harrell’s C-index and log-rank tests of Kaplan-Meier estimated survival by status for candidates listed postpolicy (November 2018 to March 2020) in the Scientific Registry of Transplant Recipients data set. The authors then developed Cox proportional hazards models and random survival forest models using prepolicy data (2010-2017). The predictor variables included age, diagnosis, laboratory measurements, hemodynamics, and supportive treatment at the time of listing. The performance of these models was compared with the candidate’s 6-status ranking in the postpolicy data.Since policy implementation, the 6-status ranking at listing has had moderate ability to rank-order candidates (C-index: 0.67). Statuses 4 and 6 had no significant difference in survival (P = 0.80), and status 5 had lower survival than status 4 (P < 0.001). Novel multivariable prediction models derived with prepolicy data ranked candidates correctly more often than the 6-status rankings (Cox proportional hazards model C-index: 0.76; random survival forest model C-index: 0.74). Objective physiologic measurements, such as glomerular filtration rate, had high variable importance.The treatment-based 6-status heart allocation system has only moderate ability to rank-order candidates by medical urgency. Predictive models that incorporate physiologic measurements can more effectively rank-order heart transplant candidates by urgency.
Angiography-Derived and Sensor-Wire Methods to Assess Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction
Authors: Roberto Scarsini, Leonardo Portolan, Francesco Della Mora, Federico Marin, Andrea Mainardi, Alessandro Ruzzarin, Molly B. Levine, Adrian P. Banning, Flavio Ribichini, Hector M. Garcia Garcia, Giovanni Luigi De Maria
Journal: JACC. Cardiovascular imaging (2023)
Myocardial Tissue-Level Characteristics of Adults With Metabolically Healthy Obesity
Authors: Hang Zhao, Rong Huang, Meng Jiang, Wei Wang, Yezi Chai, Qiming Liu, Wei Zhang, Yuchi Han, Fuhua Yan, Qifan Lu, Zhengyu Tao, Qizhen Wu, Jiang Yue, Jing Ma, Jun Pu
Journal: JACC. Cardiovascular imaging (2023)
Hemodynamic-Guided Heart Failure Management in Patients With Either Prior HF Hospitalization or Elevated Natriuretic Peptides
Authors: Akshay S. Desai, Alan Maisel, Mandeep R. Mehra, Michael R. Zile, Anique Ducharme, Sara Paul, Samuel F. Sears, Frank Smart, Kunjan Bhatt, Selim Krim, John Henderson, Nessa Johnson, Philip B. Adamson, Maria Rosa Costanzo, JoAnn Lindenfeld
Journal: JACC Heart Failure (2023)
Regional Handling and Prognostic Performance of Circulating Insulin-Like Growth Factor Binding Protein-7 in Heart Failure
Authors: Eugene S.J. Tan, Siew-Pang Chan, Yeunhyang C. Choi, Chris J. Pemberton, Richard Troughton, Katrina Poppe, Mayanna Lund, Gerry Devlin, Robert N. Doughty, A. Mark Richards
Journal: JACC Heart Failure (2023)
Exploring Ejection Fraction Range in Heart Failure Clinical Trials
Authors: Marvin A. Konstam
Journal: JACC Heart Failure (2023)

In 2018, the United Network for Organ Sharing implemented a 6-tier allocation policy to replace the prior 3-tier system. Given increasing listings of critically ill candidates for heart transplantation and lengthening waitlist times, the new policy aimed to better stratify candidates by waitlist mortality, shorten waiting times for high priority candidates, add objective criteria for common cardiac conditions, and further broaden sharing of donor hearts. There have been significant shifts in cardiac transplantation practices and patient outcomes following the implementation of the new policy, including changes in listing practices, waitlist time and mortality, transplant donor characteristics, post-transplantation outcomes, and mechanical circulatory support use. This review aims to highlight emerging trends in United States heart transplantation practice and outcomes following the implementation of the 2018 United Network for Organ Sharing heart allocation policy and to address areas for future modification.
Prevalent and Incident Anemia in PARADIGM-HF and the Effect of Sacubitril/Valsartan
Authors: James P. Curtain, Carly Adamson, Kieran F. Docherty, Pardeep S. Jhund, Akshay S. Desai, Martin P. Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Karl Swedberg, Michael R. Zile, Scott D. Solomon, Milton Packer, John J.V. McMurray
Journal: JACC Heart Failure (2023)

Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia.The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system blockers in PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure).Anemia was defined as hemoglobin <120 g/L in women and <130 g/L in men at screening. The authors investigated the effect of randomized treatment on clinical outcomes according to anemia status, change in hemoglobin from baseline, and the incidence of anemia.Of 8,239 participants with a baseline hemoglobin measurement, 1,677 (20.4%) were anemic. Patients with anemia had a more severe heart failure profile, worse kidney function, greater neurohormonal derangement, and worse clinical outcomes. Sacubitril/valsartan, compared with enalapril, decreased the risk of cardiovascular death or heart failure hospitalization similarly in patients with (HR: 0.84; 95% CI: 0.71-1.00) and without anemia (HR: 0.78 [95% CI: 0.71-0.87]; P value for interaction = 0.478). Between baseline and 12 months, hemoglobin decreased by 1.5 g/L (95% CI: 1.2-1.7 g/L) with sacubitril/valsartan compared with 2.3 g/L (95% CI: 2.0-2.6 g/L) with enalapril: mean difference 0.8 g/L (95% CI: 0.5-1.2 g/L; P < 0.001). Patients assigned to sacubitril/valsartan were less likely to develop anemia at 12 months (321 of 2,806 [11.4%]) compared with patients randomized to enalapril (440 of 2,824 [15.6%]) (OR: 0.70 [95% CI: 0.60-0.81]; P < 0.001). These findings were similar in PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) (sacubitril/valsartan vs valsartan). There was biomarker evidence of increased iron utilization with sacubitril/valsartan.Irrespective of anemia status, sacubitril/valsartan compared with enalapril, decreased mortality and hospitalization. Hemoglobin decreased less with sacubitril/valsartan and the incidence of new anemia was lower with sacubitril/valsartan. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure [PARADIGM-HF] trial; NCT01035255).
Chronic Kidney Disease, Heart Failure, and Adverse Cardiac Remodeling in Older Adults
Authors: Leo F. Buckley, Brian L. Claggett, Kunihiro Matsushita, Gearoid M. McMahon, Hicham Skali, Josef Coresh, Aaron R. Folsom, Suma H. Konety, Lynne E. Wagenknecht, Thomas H. Mosley, Amil M. Shah
Journal: JACC Heart Failure (2023)
Prognostic Value of CT-FFR–Based Functional Duke Jeopardy Score in Patients With Suspected CAD
Authors: Tong Yuan Liu, Chun Xiang Tang, Dai Min Zhang, Bo Zhang, Joseph Schoepf, Joseph P. Griffith, Hong Yan Qiao, Yi Ning Wang, Jiayin Zhang, Xiu Hua Hu, Lei Xu, Jun Hao Li, Peng Peng Xu, Yan Chun Chen, Fan Zhou, Jian Zhong, Ya Liu, Yi Xue, Yang Hou, Long Jiang Zhang
Journal: JACC. Cardiovascular imaging (2023)
Diagnostic Performance of Noninvasive Computed Tomography–Derived Fractional Flow Reserve in Patients With Severe Aortic Stenosis
Authors: Futoshi Yamanaka, Koki Shishido, Noriaki Moriyama, Tomoki Ochiai, Daisuke Sato, Eiji Koyama, Yoichi Sugiyama, Yusuke Tamaki, Takashi Yamada, Takahiro Hayashi, Hirokazu Miyashita, Hiroaki Yokoyama, Ryota Kosaki, Takayoshi Yamashita, Masashi Yamaguchi, Tamiharu Yamagishi, Takashi Matsumoto, Kazuki Tobita, Shingo Mizuno, Yutaka Tanaka, Masato Murakami, Saeko Takahashi, Kenichi Tsujita, Shigeru Saito
Journal: JACC. Cardiovascular imaging (2023)
Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice
Authors: Xiaomeng Hu, Corie Gattis, Ari G. Olroyd, Annabelle M. Friera, Kathy White, Chi Young, Ron Basco, Meghan Lamba, Frank Wells, Ramya Ankala, William E. Dowdle, August Lin, Kyla Egenberger, J. Michael Rukstalis, Jeffrey R. Millman, Andrew J. Connolly, Tobias Deuse, Sonja Schrepfer
Journal: Science Translational Medicine (2023)

Transplantation of allogeneic pancreatic donor islets has successfully been performed in selected patients with difficult-to-control insulin-dependent diabetes and impaired awareness of hypoglycemia (IAH). However, the required systemic immunosuppression associated with this procedure prevents this cell replacement therapy from more widespread adoption in larger patient populations. We report the editing of primary human islet cells to the hypoimmune HLA class I- and class II-negative and CD47-overexpressing phenotype and their reaggregation into human HIP pseudoislets (p-islets). Human HIP p-islets were shown to survive, engraft, and ameliorate diabetes in immunocompetent, allogeneic, diabetic humanized mice. HIP p-islet cells were further shown to avoid autoimmune killing in autologous, diabetic humanized autoimmune mice. The survival and endocrine function of HIP p-islet cells were not impaired by contamination of unedited or partially edited cells within the p-islets. HIP p-islet cells were eliminated quickly and reliably in this model using a CD47-targeting antibody, thus providing a safety strategy in case HIP cells exert toxicity in a future clinical setting. Transplantation of human HIP p-islets for which no immunosuppression is required has the potential to lead to wider adoption of this therapy and help more diabetes patients with IAH and history of severe hypoglycemic events to achieve insulin independence.
AI-Based Fully Automated Left Atrioventricular Coupling Index as a Prognostic Marker in Patients Undergoing Stress CMR
Authors: Théo Pezel, Philippe Garot, Solenn Toupin, Francesca Sanguineti, Thomas Hovasse, Thierry Unterseeh, Stéphane Champagne, Stéphane Morisset, Teodora Chitiboi, Athira J. Jacob, Puneet Sharma, Bharath Ambale Venkatesh, João A.C. Lima, Jérôme Garot
Journal: JACC. Cardiovascular imaging (2023)
Antisense oligonucleotide therapy for H3.3K27M diffuse midline glioma
Authors: Qian Zhang, Lucia Yang, Ying Hsiu Liu, John E. Wilkinson, Adrian R. Krainer
Journal: Science Translational Medicine (2023)

Diffuse midline gliomas (DMGs) are pediatric high-grade brain tumors in the thalamus, midbrain, or pons; the latter subgroup are termed diffuse intrinsic pontine gliomas (DIPG). The brain stem location of these tumors limits the clinical management of DIPG, resulting in poor outcomes for patients. A heterozygous, somatic point mutation in one of two genes coding for the noncanonical histone H3.3 is present in most DIPG tumors. This dominant mutation in the H3-3A gene results in replacement of lysine 27 with methionine (K27M) and causes a global reduction of trimethylation on K27 of all wild-type histone H3 proteins, which is thought to be a driving event in gliomagenesis. In this study, we designed and systematically screened 2'-O-methoxyethyl phosphorothioate antisense oligonucleotides (ASOs) that direct RNase H-mediated knockdown of H3-3A mRNA. We identified a lead ASO that effectively reduced H3-3A mRNA and H3.3K27M protein and restored global H3K27 trimethylation in patient-derived neurospheres. We then tested the lead ASO in two mouse models of DIPG: an immunocompetent mouse model using transduced mutant human H3-3A cDNA and an orthotopic xenograft with patient-derived cells. In both models, ASO treatment restored K27 trimethylation of histone H3 proteins and reduced tumor growth, promoted neural stem cell differentiation into astrocytes, neurons, and oligodendrocytes, and increased survival. These results demonstrate the involvement of the H3.3K27M oncohistone in tumor maintenance, confirm the reversibility of the aberrant epigenetic changes it promotes, and provide preclinical proof of concept for DMG antisense therapy.
Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models
Authors: Xufeng Cao, Dong Yang, Jyothi Parvathareddy, Yong-kyu Chu, Eun Jung Kim, Jhewelle N. Fitz-Henley, Xiaoyu Li, Pradeep B. Lukka, Keyur R. Parmar, Zaid H. Temrikar, Priya Dhole, Robert Scott Adcock, Jon Gabbard, Shruti Bansal, Jasper Lee, Lillian Zalduondo, Ernestine Hayes, Jennifer Stabenow, Bernd Meibohm, Elizabeth A. Fitzpatrick, Kevin Bailey, Rafael K. Campos, Justin G. Julander, Shannan L. Rossi, Donghoon Chung, Colleen B. Jonsson, Jennifer E. Golden
Journal: Science Translational Medicine (2023)

Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these viruses when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated by the 2019 outbreak of EEE disease in the United States that resulted in 38 confirmed cases, 19 deaths, and neurological effects in survivors. Here, we describe the discovery of a 2-pyrrolidinoquinazolinone scaffold, efficiently synthesized in two to five steps, whose structural optimization resulted in profound antiviral activity. The lead quinazolinone, BDGR-49, potently reduced cellular VEEV and EEEV titers by >7 log at 1 μM and exhibited suitable intravenous and oral pharmacokinetic profiles in BALB/c mice to achieve excellent brain exposure. Outstanding in vivo efficacy was observed in several lethal, subcutaneous infection mouse models using an 8-day dosing regimen. Prophylactically administered BDGR-49 at 25 mg kg